dbSNP rs468646: MX1:c.436+127A>C (chr21-41437279-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002462.5(MX1):c.436+127A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 969,452 control chromosomes in the GnomAD database, including 96,358 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 12139 hom., cov: 31)

Exomes 𝑓: 0.43 ( 84219 hom. )

Consequence

MX1
NM_002462.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.776

Publications

5 publications found

Variant links:

Genes affected

MX1 (HGNC:7532): (MX dynamin like GTPase 1) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that participates in the cellular antiviral response. The encoded protein is induced by type I and type II interferons and antagonizes the replication process of several different RNA and DNA viruses. There is a related gene located adjacent to this gene on chromosome 21, and there are multiple pseudogenes located in a cluster on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

MX1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5 link	c.436+127A>C		intron_variant	Intron 7 of 16	ENST00000398598.8	NP_002453.2	P20591-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8 link	c.436+127A>C		intron_variant	Intron 7 of 16	1	NM_002462.5	ENSP00000381599.3		P20591-1

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

56557

AN:

151902

Hom.:

12142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.325

Gnomad EAS

AF:

0.00732

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.501

Gnomad OTH

AF:

0.370

GnomAD4 exome

AF:

0.430

AC:

351289

AN:

817432

Hom.:

84219

AF XY:

0.427

AC XY:

178305

AN XY:

418028

show subpopulations

African (AFR)

AF:

0.199

AC:

4018

AN:

20166

American (AMR)

AF:

0.242

AC:

6954

AN:

28680

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

5156

AN:

16302

East Asian (EAS)

AF:

0.00376

AC:

137

AN:

36470

South Asian (SAS)

AF:

0.265

AC:

14661

AN:

55252

European-Finnish (FIN)

AF:

0.475

AC:

20544

AN:

43276

Middle Eastern (MID)

AF:

0.317

AC:

1346

AN:

4252

European-Non Finnish (NFE)

AF:

0.493

AC:

283441

AN:

574960

Other (OTH)

AF:

0.395

AC:

15032

AN:

38074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

8968

17936

26904

35872

44840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5978

11956

17934

23912

29890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.372

AC:

56573

AN:

152020

Hom.:

12139

Cov.:

AF XY:

0.367

AC XY:

27302

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.215

AC:

8937

AN:

41474

American (AMR)

AF:

0.308

AC:

4702

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.325

AC:

1128

AN:

3472

East Asian (EAS)

AF:

0.00715

AC:

AN:

5178

South Asian (SAS)

AF:

0.265

AC:

1278

AN:

4824

European-Finnish (FIN)

AF:

0.483

AC:

5092

AN:

10550

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.501

AC:

34016

AN:

67938

Other (OTH)

AF:

0.370

AC:

779

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1665

3330

4995

6660

8325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.430

Hom.:

9618

Bravo

AF:

0.350

Asia WGS

AF:

0.154

AC:

537

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.6

(source)

DANN

Benign

0.75

PhyloP100

0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over